Objectives To compare simplified monitoring methods to standard of care monitoring, both in combination with intensive adherence counselling, in the treatment of HIV disease in resource limited settings. To evaluate the different frequency of clinical visit and laboratory monitoring. To evaluate the reduced-cost CD4 testing using the technique of CD4 cell depletion with automated cell counting developed at the HIV-NAT laboratory. Specific aims To evaluate simplified monitoring in patients treated with antiretroviral therapy in resource limited settings To build infrastructure and capacity for HIV monitoring in primary and secondary care hospitals in Thailand and Cambodia To promote adherence to antiretroviral therapy by counselling and questionnaire at every clinic visit and pill counts. To validate the technique of simplified magnetic CD4 cells depletion with automated cell counter and assess feasibility of implementation at regional hospitals in Thailand including Cambodia. Methods The study will be conducted in primary and secondary care hospitals in Thailand and Cambodia. Nine hundred thirty-two antiretroviral na'fve HIV-infected adults with CD4 <200 cells/mm 3 or CDC clinical classification B or C without active opportunistic infections will be equally randomized in a 2 x 2 factorial design to four groups to be monitored by either CD4 and clinical outcome, or CD4 and clinical outcome plus viral load, and followed-up every 8 weeks or every 16 weeks. Patients in each arm will receive the same antiretroviral therapy. Clinical and immunological monitoring will be performed every 8 weeks or every 16 weeks assigned by randomization, and virological monitoring will be performed every 16 weeks. Primary endpoint Primary endpoint is the proportion of patient with CD4 >200 cells/mm 3 at week 144 of study.